# US 5,710,268 A · Process for the preparation of methylated cyclodextrin derivatives, and their use as solubilizers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,710,268 A - Document ID: US5710268A - Status: Granted - Kind: A - Application number: 08/308,376 - Filed: 1994-09-14 - Granted: 1998-01-20 - Earliest claimed: 1993-10-01 - Assignees: Consortium fur Elektrochemische Industrie GmbH - Inventors: Thomas Wimmer - Web page: https://patentgrep.com/patent/US5710268A ## CPC - C08B 37/0012: {Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof} - C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21) ## Abstract A process in which .alpha.-, .beta.- and/or .gamma.-cyclodextrin are reacted in a suitable base, with a suitable O-alkylating agent and, where appropriate, following neutralization of the reaction mixture, the resulting alkylated cyclodextrin derivatives are subsequently separated, out of the reaction mixture, wherein .alpha.-, .beta.- and/or .gamma.-cyclodextrin are initially dissolved in a portion of the base and the O-alkylation agent and further base are added subsequently. ## Claims ### Claim 1 A process for the preparation of a methylated cyclodextrin selected from the group consisting of a methylated .alpha.-cyclodextrin, a methylated .beta.-cyclodextrin, a methylated .gamma.-cyclodextrin and the mixtures thereof, which process has a total reaction time of about 5-30 hours, comprising initially dissolving an .alpha.-, .beta.-, or .gamma.-cyclodextrin or mixture thereof in a portion of a base and subsequently adding methyl chloride as an O-alkylation agent and additional base simultaneously and continuously during a period of time up to two-thirds of the total reaction time; reacting the .alpha.-, .beta.-, or .gamma.-cyclodextrin or mixture thereof in said base with said methyl chloride O-alkylating agent to produce a reaction mixture; and separating the resulting methylated cyclodextrin derivatives out of the reaction mixture. ### Claim 2 A process for the preparation of a methylated cyclodextrin selected from the group consisting of a methylated .alpha.-cyclodextrin, a methylated .beta.-cyclodextrin, a methylated .gamma.-cyclodextrin and the mixtures thereof, which process has a total reaction time of about 5-30 hours, comprising initially dissolving an .alpha.-cyclodextrin, a .beta.-cyclodextrin, or a .gamma.-cyclodextrin or mixture thereof in from 1 to 5 mol portion of an aqueous solution of a base in a concentration of 5-20% (w/w) per mol of cyclodextrin, and from 15 to 25 mol of methyl chloride as an O-alkylating agent, up to a maximum base concentration of from 15 to 25 mol per mol of cyclodextrin; subsequently adding additional base and said methyl chloride O-alkylating agent simultaneously and continuously during a period of time up to two-thirds of the total reaction time; reacting the .alpha.-cyclodextrin, .beta.-cyclodextrin or .gamma.-cyclodextrin in said base with said methyl chloride O-alkylating agent to produce a reaction mixture; and separating the resulting methylated cyclodextrin derivatives out of the reaction mixture. ### Claim 3 (depends on 1) The process as Claimed in claim 1, comprising adding the O-alkylating agent and the additional base simultaneously and continuously. ### Claim 4 (depends on 1) The process as claimed in claim 1, wherein said base is selected from the group consisting of potassium hydroxide and sodium hydroxide. ### Claim 5 Methyl cyclodextrin having an average degree of substitution (DS), measured by means of .sup.1 H-NMR spectroscopy, between 1.7 and 1.9 and the O6 position is methylated to the extent of from 55 to 75%. ### Claim 6 Methyl-.beta.-cyclodextrin having an average degree of substitution (DS), measured by means of .sup.1 -NMR spectroscopy, between 1.7 and 1.9 and having an average degree of methylation of the O2 and O6 positions of from 60 to 70%. ### Claim 7 Methyl-.gamma.-cyclodextrin having an average degree of substitution (DS), measured by means of .sup.1 H-NMR spectroscopy, of between 1.7 and 1.9 and having an average degree of methylation of the O2 and the O6 positions of from 60 to 70%. ### Claim 8 Methyl-.alpha.-cyclodextrin having an average degree of substitution (DS), measured by means of .sup.1 H-NMR spectroscopy, of between 1.7 and 1.9 and having an average degree of methylation of the O2 position of from 70 to 80% and having an average degree of methylation of the O6 position of from 60 to 70%. ### Claim 9 (depends on 5) In a method for solubilizing substances which are difficult to dissolve in water, the improvement comprising utilizing the methylated cyclodextrin derivatives of claim 5 for solubilizing said difficult to dissolve substances. ### Claim 10 (depends on 6) In a method for solubilizing substances which are difficult to dissolve in water, the improvement comprising utilizing the methyl-.beta.-cyclodextrin of claim 6 for solubilizing said difficult to dissolve substances. ### Claim 11 (depends on 7) In a method for solubilizing substances which are difficult to dissolve in water, the improvement comprising utilizing the methyl-.gamma.-cyclodextrin of claim 7 for solubilizing said difficult to dissolve substances. ### Claim 12 (depends on 8) In a method for solubilizing substances which are difficult to dissolve in water, the improvement comprising utilizing the methyl-.alpha.-cyclodextrin of claim 8 for solubilizing said difficult to dissolve substances. ### Claim 13 (depends on 1) The process as claimed in claim 1, wherein more than 200 g of said cyclodextrin derivatives are dissolvable in 100 ml of water over a temperature range of from 20.degree. to 100.degree. C. ### Claim 14 (depends on 2) The process as claimed in claim 2, wherein more than 200 g of said cyclodextrin derivatives are dissolvable in 100 ml of water over a temperature range of from 20.degree. to 100.degree. C. ### Claim 15 (depends on 1) The process as claimed in claim 1, wherein the solubility of the cyclodextrin derivatives in water increases with increasing temperature up to 250 g/100 ml of H.sub.2 O. ### Claim 16 (depends on 2) The process as claimed in claim 2, wherein the solubility of the cyclodextrin derivatives in water increases with increasing temperature up to 250 g/100 ml of H.sub.2 O.